title: Structural and thermodynamic dissection of linear motif recognition by the E. coli sliding clamp.
abstract: Protein-protein interactions based on linear motif (LM) recognition play roles in many cell regulatory processes. The E. coli sliding clamp is a protein mediator of replisome formation, which uses a common surface pocket composed of two subsites (I and II) to interact with LMs in multiple binding partners. A structural and thermodynamic dissection of sliding clamp-LM recognition has been performed, providing support for a sequential binding model. According to the model, a hydrophobic C-terminal LM dipeptide submotif acts as an anchor to establish initial contacts within subsite I, and this is followed by formation of a stabilizing hydrogen-bonding network between the flanking LM residues and subsite II. Differential solvation/desolvation during positioning of the submotifs is proposed as a driver for the sequential binding. Our model provides general insights into linear motif recognition and should guide the design of small-molecule inhibitors of the E. coli sliding clamp, an emerging antibacterial target.
authors.affiliation: School of Chemistry, University of Wollongong , Northfields Avenue, Wollongong 2522, NSW, Australia.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelso
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beck
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Oakley
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins